Amyloid β binds procaspase-9 to inhibit assembly of Apaf-1 apoptosome and intrinsic apoptosis pathway.

Document Type

Article

Publication Date

4-2014

Publication Title

Biochimica et Biophysica Acta

Abstract

Apoptosis is essential in the death process induced by Amyloid-β (Aβ), a major constituent of diffuse plaques found in Alzheimer's disease patients. However, we have found that caspase activation and cell death induced by staurosporine, employed to induce the intrinsic mitochondria-dependent apoptotic pathway, were significantly reduced by 42 amino-acid Aβ42, implying that the peptide also has a negative effect on the apoptotic process. The inhibitory effect of Aβ42 on the apoptotic pathway is associated with its interaction with procaspase-9 and consequent inhibition of Apaf-1 apoptosome assembly. We detected the inhibitory effect in the early stage (<8h) of apoptosis, but later caspase activation becomes obvious. Thus we inferred that the inhibitory process on apoptosis begins at an early stage, and the later robust activation surpasses it. We propose that the apoptotic manifestation in Aβ-treated cells is a combined consequence of those anti- and pro-apoptotic processes.

Volume

1843

Issue

4

First Page

685

Last Page

693

DOI

10.1016/j.bbamcr.2014.01.008

ISSN

0006-3002

PubMed ID

24424093

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